The primary objective of the proposal is to study the mechanism(s) by which tumors avoid destruction and to find ways to reverse such escape using as the starting point a well-defined model of BCG potentiated antitumor immunity (Hawrylko, E., Mackaness, G.B., J. Natl. Cancer Inst. 51: 1677-82, 1973). Experiments will demonstrate whether or not BCG potentiated immunity is subject to the same regulatory mechanisms which occur in normal animals and allow escape. In vivo and in vitro experiments will attempt to define the locus of "blocking" which allows tumor escape, i.e. at the inductive stage of immunization (afferent) or the effector stage (efferent limb), the cells involved and the sequence of events. Splenectomy, intravenous BCG and cyclophosphamide alone or in combination will be used to delineate the parameters of the "blocking" mechanism and ways to eliminate it. Baseline information will be obtained using the poorly immunogenic, methylcholanthrene induced murine mastocytoma, P 815, and the more highly antigenic sarcoma, Meth. A. If such studies are fruitful, the mouse mammary tumor virus (MTV) system will be approached in parallel experiments.